We propose to attempt to correlate the progressive loss of normal circadian rhythmicity experienced by the aging female rat with a structural analysis of the afferent organization of the suprachiasmatic nuclei (SCN) of the animal. In previous studies, we have described a progressive degeneration in the ability of the aging rat to display normal circadian rhythms. This progressive loss of normal circadian rhythmicity may reflect a loss of normal input from either the visual system or the raphe to the primary circadian locus in the rat, the SCN. Our first specific aim is to quantitate changes in the cell number as well as the axo-somatic and axo-dendritic terminals in the SCN of the aging rat. We will also quantitate changes in the synaptic connections between optic neurons and SCN neurons. By employing immunocytochemistry, we will describe qualitative changes in the pre- or postsynaptic cells in the afferent connections of the SCN of aging rats which are immunoreactive for neuropeptide Y, serotonin, vasoactive intestinal polypeptide, gastrin releasing peptide or bombesin. Behavioral and physiological data on a variety of circadian rhythms from young and aging rats will be collected prior to sacrifice. The proposed studies appear to be the first to correlate age- related changes in physiological and behavioral rhythms with changes in the structural integrity of the SCN of those animals. As mounting evidence in the literature indicates that deficits in the circadian system have a critical role in the etiology of a number of diseases, including a variety of forms of mental illness, it is imperative that we more fully understand the neuroanatomy of the SCN. The aging female rat undergoing progressive loss of normal circadian function can serve as a powerful model in the search for understanding the basis of a number of forms of mental illness.